miR-204-5p通过靶向负性调控RAB22A促进膀胱癌细胞的恶性生物学行为  

High expression of miR-204-5p promotes malignant behaviors of bladder cancer cells by negatively regulating RAB22A

作　　者：李立强 郭园园 王成勇 常睿 孙巍 高五岳 王超[2] 刘贝贝 Liqiang LI;Yuanyuan GUO;Chengyong WANG;Rui CHANG;Wei SUN;Wuyue GAO;Chao WANG;Beibei LIU(Department of Urology,First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,China;Department of Anesthesiology,Bozhou People's Hospital,Bozhou 236000,China)

机构地区：[1]蚌埠医科大学第一附属医院泌尿外科,安徽蚌埠233004 [2]亳州市人民医院麻醉科,安徽亳州236000

出　　处：《南方医科大学学报》2024年第11期2235-2242,共8页Journal of Southern Medical University

基　　金：安徽省教育厅自然科学研究重点项目(KJ2021A0706);安徽省卫健委科研项目重点课题(AHWI2021a007);蚌埠医学院科技项目(2020bypd008);蚌埠医学院附属第一医院杰青项目(2019byyfyyq01);蚌埠医学院“512”中青年骨干教师培养计划(51202307)。

摘　　要：目的探讨MiR-204-5p靶向RAB22A对膀胱癌细胞生物学行为的影响及其分子机制。方法TCGA数据库进行了miR-204-5p的生存分析和临床病理性状的相关性分析;检测膀胱癌组织和癌旁组织以及正常尿路上皮细胞和膀胱癌细胞中miR-204-5p的表达水平;过表达/敲低miR-204-5p后检测细胞增殖、迁移和侵袭、和凋亡等变化;转录组测序,数据库分析和多种实验证实miR-204-5p靶向抑制RAB22A基因调控膀胱癌细胞的生物学行为。结果TCGA数据库中MiR-204-5p高表达患者的中位生存期较低,表现出较差的预后(P<0.05);miR-204-5p在膀胱癌组织和细胞表达明显上调(P<0.05);过表达miR-204-5p可促进细胞增殖(P<0.05)、迁移和侵袭(P<0.05),减少细胞凋亡(P<0.05),敲低后则相反;转录组测序,数据库分析和双荧光素酶实验提示RAB22A是miR-204-5p下游关键因子,qRT-PCR,Western blotting证实过表达miR-204-5p可抑制RAB22A的表达(P<0.05);过表达RAB22A可部分逆转miR-204-5p对膀胱癌细胞生长的促进作用(P<0.05)。结论miR-204-5p通过靶向负性调控RAB22A促进膀胱癌细胞的恶性生物学行为。Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

关 键 词：miR-204-5p RAB22A 膀胱癌 

分 类 号：R737.9[医药卫生—肿瘤]